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IgG Antibodies to Pneumococcal Serotypes 1 and 5 in Relation to PCV13 Vaccination Status in Children Aged Under 5 Years in Lao PDR: A Cross-Sectional Survey
Background/Objectives: Pneumococcal serotypes 1 and 5 are associated with invasive pneumococcal disease (IPD). However, data on the circulation of these serotypes in Asia following the introduction of the pneumococcal conjugate vaccine (PCV) is limited. The Lao People’s Democratic Republic (Lao PDR) introduced PCV13 into its national immunisation programme in 2013. We undertook a serosurvey to assess the IgG responses to serotypes 1 and 5 from a convenience sample of children aged under 5 years in Vientiane, Lao PDR. Methods: This cross-sectional analysis used a convenience sample of the close contacts of children under five years old who had been hospitalised with acute respiratory infections between 2013 and 2016 in Vientiane, Lao PDR. Serotype-specific IgG concentrations to serotypes 1 and 5 were measured using a modified WHO ELISA method. Results: A total of 214 participants were included, 130 of whom were unvaccinated and 84 were vaccinated with PCV13. Compared to unvaccinated participants, a higher number of PCV-vaccinated participants met the IgG threshold for IPD (≥0.35 μg/mL) [41.5% (54/130) vs. 71.4% (60/84)] for serotype 1. In contrast, for serotype 5, a similar number of participants in the PCV-vaccinated and unvaccinated group met the IgG threshold for IPD (85.7% (72/84) vs. 82.3% (107/130). Among unvaccinated children, serotype 1 IgG levels peaked at 12 and 23 months at 0.49 µg/mL (95% CIs: 0.25–0.96), while serotype 5 IgG levels were similar across age groups, ranging from 0.55 to 0.79 µg/mL. Conclusions: Our findings indicate the considerable circulation of serotypes 1 and 5 within the community in Lao PDR. Ongoing surveillance is important for informing PCV vaccination strategies.
Detection of Mycoplasma pneumoniae in hospitalized children with pneumonia in Laos
Mycoplasma pneumoniae has been described worldwide as an important cause of community-acquired pneumonia. From December 2013 to December 2014, 461 children admitted to Mahosot Hospital, Vientiane, Laos, with acute respiratory infection were investigated for upper respiratory microorganisms using probe-based real-time polymerase chain reaction (PCR) (FTD33). M. pneumoniae was detected by FTD33 in the upper respiratory tract of three patients, two girls and one boy, 5.7 and 3.9 years old and 13.6 years old, respectively. They presented with clinical features compatible with M. pneumoniae infection. They improved without M. pneumoniae directed therapy. The two girls were also positive for other potential pathogens. The boy had abnormal pulmonary auscultation, and one of the girls had significant anaemia. These results suggest that enhancement of diagnostic systems for M. pneumoniae detection is needed to improve understanding of the epidemiology of M. pneumoniae infection in Laos.
Direct real-time RT-PCR for the detection of dengue virus from patient serum in Lao PDR
Introduction Dengue fever is a growing global concern with an estimated 100–400 million infections every year and rising mortality over the past decade. In 2017, 40,000 deaths were attributed to dengue. Real-time reverse transcription PCR (RT-qPCR) is the gold standard technique to detect dengue virus (DENV) during the acute phase of the infection. However, it requires prior RNA purification which is costly and time consuming. We evaluated direct RT-qPCR using Luna Universal Probe One-Step RT-qPCR kit (Luna RT-qPCR) for the detection of DENV in sera. Methods Luna RT-qPCR conditions were optimized using DENV2 isolates. The efficiency of direct Luna RT-qPCR was evaluated on a panel of 132 patient sera using RNA purification (EZ1&2 Virus Mini Kit) followed by RT-qPCR (SuperScript III Platinum One-Step qRT-PCR system) as reference standard. Results The sensitivity (95% CI) of direct Luna RT-qPCR using neat patient sera was 34% (25–45). By reducing PCR inhibitors through a 1/10 dilution of the sera, the sensitivity improved to 86% (95% CI: 77–92). Comparable results were obtained between direct Luna RT-qPCR and reference standard process for samples with Cq < 35. Conclusion The results obtained in this study are promising. Direct RT-qPCR for DENV detection in patient sera, could make PCR-based dengue detection and typing, and potentially other target detections, more affordable for reference laboratories in LMICs by reducing reagent cost by approximately two-thirds. Further studies are needed to evaluate DENV direct RT-qPCR on prospective samples in diagnosis context and to improve the sensitivity by minimizing the impact of inhibitors.
A subpopulation of high IL-21-producing CD4+ T cells in Peyer’s Patches is induced by the microbiota and regulates germinal centers
AbstractThe production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP+, high IL-21 producing Tfh cells present only in Peyer’s Patches. GFP+Tfh cells were found to be polyclonal and related to GFP−Tfh cells of Peyer’s Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP+Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4+ T cells and B cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer’s Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4+ Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.
Case Report: Herpes simplex virus type 2 (HSV-2) meningo-encephalitis associated with traumatic brain injury – a case report from Lao PDR
Background Neurological symptoms following head trauma are common; however, the cause may not always be obvious. In the absence of open wounds, fractures, or surgical interventions, infectious causes may not be considered, and investigations may not be targeted to investigate this possibility. Case A 39-year-old male presented with a severe headache, reduced consciousness, and confusion. Two days earlier, he had been discharged from the hospital, where he had been treated for traumatic brain injury with subarachnoid hemorrhage following a road traffic accident. Herpes simplex virus type 2 (HSV-2) was detected in the cerebrospinal fluid, confirming the diagnosis of viral meningoencephalitis. He was treated with oral aciclovir for two weeks and achieved full neurological recovery. Conclusions This case highlights the risk of viral reactivation following trauma, particularly head injuries. Central nervous system infections should be considered in cases of delayed deterioration following trauma. The optimal treatment of herpes simplex virus (HSV) encephalitis may be challenging in resource-limited settings.
Consensus Statements on Airway Clearance Interventions in Intubated Critically Ill Patients-Protocol for a Delphi Study.
Intubated critically ill patients are susceptible to secretion accumulation because of compromised airway clearance. Various airway clearance interventions are employed to prevent complications arising from mucus retention. This Delphi study aims to collect global opinions in an international expert panel of ICU professionals on the usefulness of these various airway clearance interventions. A steering committee performed a literature search informing the formulation of statements. Statements are grouped into two distinct parts: (1) Humidification and Nebulization, and (2) Suctioning and Mucus mobilization techniques. For each part, a diverse panel of 30-40 experts will be selected, with concerted effort to involve experts from various medical specialties involved in airway clearance methods. Multiple choice questions (MCQs) or 7-point Likert-scale statements will be used in the iterative Delphi rounds to reach consensus on various airway clearance interventions. Rounds will continue until stability is achieved for all statements. Consensus will be deemed achieved when a choice in MCQs or a Likert-scale statement achieves ≥75% agreement or disagreement. Starting from the second round of the Delphi process, stability will be assessed using non-parametric χ2 tests or Kruskal-Wallis tests. Stability will be defined by a p-value of ≥0.05.
VENTIlatory strategies for patients with severe traumatic brain injury in the LOw- and Middle-Income CountrieS. The VENTILOMICS survey.
To revisit the VENTIlatory Strategies for Patients with Severe Traumatic Brain Injury (VENTILO) survey, focusing on ventilatory management practices among healthcare professionals in low- and middle-income countries. A cross-sectional on-line survey, VENTIlatory strategies for patients with severe traumatic brain injury in the LOw- and Middle-Income CountrieS (VENTILOMICS), was conducted using the original VENTILO survey questionnaire, developed following a review of literature on respiratory management in traumatic brain injury patients, captured demographics of participants, type of hospital/specialty and available neuromonitoring tools; protocols for mechanical ventilation and weaning, and respiratory management strategies. Descriptive statistics were computed for all study variables. We analyzed data based on the economic status of the low- and middle-income countries. There were 204 respondents from 28 low- and middle-income countries. Our results indicate that 55 - 70% of respondents recommend tidal volumes of 6 - 8mL/kg for patients with high or medium partial pressure of arterial oxygen/inspired fraction of oxygen, while tidal volumes of 4 - 6mL/kg is preferred for those with low partial pressure of arterial oxygen/inspired fraction of oxygen ratios. For patients with intracranial hypertension, lower positive end-expiratory pressure levels were utilized. The findings suggest a consistent approach to lung-protective ventilation across low-and middle-income countries, with notable variations influenced by local resources and economic status. This study highlights the necessity for tailored research and guidelines to address the specific challenges faced in traumatic brain injury management within low-and middle-income countries.
Dosing interval is a major factor determining the quality of T cells induced by SARS-CoV-2 mRNA and adenoviral vector vaccines
Functional T cell responses are crucial for protective immunity induced by COVID-19 vaccination, but factors influencing the quality of these responses are incompletely understood. We used an activation-induced marker (AIM) assay and single-cell transcriptomic sequencing to analyze SARS-CoV-2 spike-responsive T cells after mild SARS-CoV-2 infection or after one or two doses of mRNA–lipid nanoparticle (mRNA-LNP) or adenoviral-vectored COVID-19 vaccines. Our findings revealed broad functional and clonal heterogeneity in T cells generated by vaccination or infection, including multiple distinct effector populations. T cell function was largely conserved between COVID-19 vaccine platforms but was distinct compared with SARS-CoV-2 infection. Notably, the dosing interval greatly influenced the quality of T cells after two vaccine doses, particularly after mRNA-LNP vaccination, where a longer interval led to reduced inflammatory signaling and increased secondary proliferation. These insights enhance our understanding of SARS-CoV-2–specific T cells and inform the optimization of mRNA vaccination regimens.
MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines
Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses and reactogenicity, but underpinning mechanisms remain unclear. We longitudinally compared homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination, focusing on cytokine-responsive innate-like lymphocytes—mucosal-associated invariant T (MAIT) cells and Vδ2 + γδ T cells—which sense and tune innate-adaptive cross-talk. Ad priming elicited robust type I interferon (IFN)–mediated innate-like T cell activation, augmenting T cell responses (innate-to-adaptive signaling), which was dampened at boost by antivector immunity. Conversely, mRNA boosting enhanced innate-like responses, driven by prime-induced spike-specific memory T cell–derived IFN-γ (adaptive-to-innate signaling). Extending the dosing interval dampened inflammation at boost because of waning T cell memory. In a separate vaccine trial, preboost spike-specific T cells predicted severe mRNA reactogenicity regardless of the priming platform or interval. Overall, bidirectional innate-like and adaptive cross-talk, and IFN-γ–licensed innate-like T cells, orchestrate interval-dependent early vaccine responses, suggesting modifiable targets for safer, more effective regimens.
Manipulation of the microbiome in critical illness-probiotics as a preventive measure against ventilator-associated pneumonia.
ObjectiveTo describe the possible modes of action of probiotics and provide a systematic review of the current evidence on the efficacy of probiotics to prevent ventilator-associated pneumonia (VAP) in critically ill patients.MethodsWe conducted an unrestricted search of the English language medical literature. For each individual study, the relative risk of VAP was calculated using the reported primary outcome data.ResultsThe search identified a total of 72 articles. Eight articles enrolling a total of 1229 patients fulfilled the inclusion and exclusion criteria. In four trials, the investigators were blinded for the intervention, and two trials used an intention-to-treat analysis. Loss to follow-up with regard to the primary endpoint ranged from 0 to 14% in the intervention groups and from 0 to 16% in the control groups. The incidence of VAP expressed as the percentage of studied patients was reported in seven trials. The incidence of VAP ranged from 4 to 36% in the intervention groups and from 13 to 50% in the control groups. The relative risk for VAP ranged between 0.30 and 1.41. Three trials showed a significant difference in favor of probiotic therapy between the intervention and the control groups.ConclusionsThe incidence of VAP tended to be lower in patients treated with probiotics in most trials identified by the systematic search. Due to the heterogeneity of the studies and the low quality of evidence, it remains difficult to draw firm conclusions. The efficacy of preventive probiotics should be studied in more detail in future trials. Application of probiotics for the prevention of VAP seems to be safe with only few side effects reported in the selected trials.
ERS International Congress, Madrid, 2019: highlights from the Respiratory Intensive Care Assembly.
The Respiratory Intensive Care Assembly of the European Respiratory Society is delighted to present the highlights from the 2019 International Congress in Madrid, Spain. We have selected four sessions that discussed recent advances in a wide range of topics: from acute respiratory failure to cough augmentation in neuromuscular disorders and from extra-corporeal life support to difficult ventilator weaning. The subjects are summarised by early career members in close collaboration with the Assembly leadership. We aim to give the reader an update on the most important developments discussed at the conference. Each session is further summarised into a short list of take-home messages.
Impact of Country Income Level on Outcomes in Patients with Acute Brain Injury Requiring Invasive Mechanical Ventilation: A Secondary Analysis of the ENIO Study.
BackgroundInvasive mechanical ventilation can present complex challenges for patients with acute brain injury (ABI) in middle-income countries (MICs). We characterized the impact of country income level on weaning strategies and outcomes in patients with ABI.MethodsA secondary analysis was performed on a registry of critically ill patients with ABI admitted to 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Patients were classified as high-income country (HIC) or MIC. The primary outcome was ICU mortality. Secondary outcomes were days to first extubation, tracheostomy, extubation failure, ICU length of stay, and hospital mortality. Multivariable analyses were adjusted for clinically preselected covariates such as age, sex, body mass index, neurological severity, comorbidities, and ICU management. Extubation and tracheostomy outcomes were also adjusted for arterial blood gas values and ventilatory settings.ResultsOf 1512 patients (median age = 54 years, 66% male), 1170 (77%) were from HICs, and 342 (23%) were from MICs. Median age was significantly lower in MICs [35 (range 26-52) vs. 58 (range 45-68) years in HICs]. Neurosurgical procedures (47.7% vs. 38.2%) and decompressive craniectomy (30.7% vs. 15.9%) were more common in MICs, whereas intracranial pressure monitoring (12.0% vs. 51.5%) and external ventricular drain (7.6% vs. 35.6%) were less common. Compared with HICs, patients from MICs had 2.27 times the odds of ICU mortality [p = 0.009, 95% confidence interval (CI) 1.22-4.21]. Frequency of extubation failure was lower in MICs but not significant after adjustment. Patients from MICs had 3.38 times the odds of tracheostomy (p ≤ 0.001, 95% CI 2.28-5.01), 5.59 days shorter mean ICU stay (p ConclusionsIn an international registry of patients with ABI requiring invasive mechanical ventilation, MICs had higher odds of ICU mortality, tracheostomy placement, and hospital mortality compared with HICs, which may be due to difference in neurocritical care resources and management.
Individual and combined effects of chemical and mechanical power on postoperative pulmonary complications: a secondary analysis of the REPEAT study.
IntroductionIntra-operative supplemental oxygen and mechanical ventilation expose the lungs to potentially injurious energy. This can be quantified as 'chemical power' and 'mechanical power', respectively. In this study, we sought to determine if intra-operative chemical and mechanical power, individually and/or in combination, are associated with postoperative pulmonary complications.MethodsUsing an individual patient data analysis of three randomised clinical trials of intra-operative ventilation, we summarised intra-operative chemical and mechanical power using time-weighted averages. We evaluated the association between intra-operative chemical and mechanical power and a collapsed composite of postoperative pulmonary complications using multivariable logistic regression to estimate the odds ratios related to the effect of 1 J.min-1 increase in chemical or mechanical power with adjustment for demographic and intra-operative characteristics. We also included an interaction term to assess for potential synergistic effects of chemical and mechanical power on postoperative pulmonary complications.ResultsOf 3837 patients recruited to three individual trials, 2492 with full datasets were included in the analysis. Intra-operative time-weighted average (SD) chemical power was 10.2 (3.9) J.min-1 and mechanical power was 10.5 (4.4) J.min-1. An increase of 1 J.min-1 in chemical power was associated with 8% higher odds of postoperative pulmonary complications (OR 1.08, 95%CI 1.05-1.10, p DiscussionBoth chemical and mechanical power are independently associated with postoperative pulmonary complications. Further work is required to determine causality.
Right Ventricular Injury Definition and Management in Veno-Venous Extracorporeal Membrane Oxygenation.
Right ventricular injury (RVI) in respiratory failure receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is associated with significant mortality. A scoping review is necessary to map the current literature and guide future research regarding the definition and management of RVI in patients receiving VV ECMO. We searched for relevant publications on RVI in patients receiving VV ECMO in Medline, EMBASE, and Web of Science. Of 1,868 citations screened, 30 studies reported on RVI (inclusive of right ventricular dilation, right ventricular dysfunction, and right ventricular failure) during VV ECMO. Twenty-three studies reported on the definition of RVI including echocardiographic indices of RV function and dimensions, whereas 13 studies reported on the management of RVI, including veno-pulmonary (VP) ECMO, veno-arterial (VA) ECMO, positive inotropic agents, pulmonary vasodilators, ultra-lung-protective ventilation (Ultra-LPV), and optimization of positive end-expiratory pressure (PEEP). The definitions of RVI in patients receiving VV ECMO used in the literature are heterogeneous. Despite the high incidence of RVI during VV ECMO support and its strong association with mortality, studies investigating therapeutic strategies for RVI are also lacking. To fill the existing knowledge gaps, a consensus on the definition of RVI and research investigating RV-targeted therapies during VV ECMO is urgently warranted.
Medical Triage: Ethical Implications and Management Strategies.
Natural or man-made medical disasters have repeatedly affected human communities. The impact on health care resources may vary depending on the magnitude of each crisis, catastrophe or pandemic, and the resources available. Medical triage protocols serve as invaluable tools to address clinical needs, particularly when resources, including supplies, equipment, and personnel, are limited. Although resources should be allocated to maximize the benefit, resource allocations need to be ethically sound. Existing triage protocols have inherent limitations.
Respiratory mechanics and mechanical power during low vs. high positive end-expiratory pressure in obese surgical patients - A sub-study of the PROBESE randomized controlled trial.
Study objectiveWe aimed to characterize intra-operative mechanical ventilation with low or high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) regarding intra-tidal recruitment/derecruitment and overdistension using non-linear respiratory mechanics, and mechanical power in obese surgical patients enrolled in the PROBESE trial.DesignProspective, two-centre substudy of the international, multicentre, two-arm, randomized-controlled PROBESE trial.SettingOperating rooms of two European University Hospitals.PatientsForty-eight adult obese patients undergoing abdominal surgery.InterventionsIntra-operative protective ventilation with either PEEP of 12 cmH2O and repeated RM (HighPEEP+RM) or 4 cmH2O without RM (LowPEEP).MeasurementsThe index of intra-tidal recruitment/de-recruitment and overdistension (%E2) as well as airway pressure, tidal volume (VT), respiratory rate (RR), resistance, elastance, and mechanical power (MP) were calculated from respiratory signals recorded after anesthesia induction, 1 h thereafter, and end of surgery (EOS).Main resultsTwenty-four patients were analyzed in each group. PEEP was higher (mean ± SD, 11.7 ± 0.4 vs. 3.7 ± 0.6 cmH2O, P 2O, P T and RR did not differ significantly (7.3 ± 0.6 vs. 7.4 ± 0.8 ml∙kg-1, P = 0.835; and 14.6 ± 2.5 vs. 15.7 ± 2.0 min-1, P = 0.150, respectively). %E2 was higher in HighPEEP+RM than in LowPEEP following induction (-3.1 ± 7.2 vs. -12.4 ± 10.2%; P 2O∙l∙s-2, P = 0.009; and 15.7 ± 5.5 vs. 28.5 ± 8.4 cmH2O∙l, P -1, P ConclusionsIn this sub-cohort of PROBESE, intra-operative ventilation with high PEEP and RM reduced intra-tidal recruitment/de-recruitment as well as driving pressure, elastance, resistance, and mechanical power, as compared with low PEEP.Trial registrationThe PROBESE study was registered at www.Clinicaltrialsgov, identifier: NCT02148692 (submission for registration on May 23, 2014).
European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.
PurposeLower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes.MethodsA prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups.Results1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates.ConclusionVHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.